Dose intensification of proton radiation therapy led to improved overall survival for patients with newly diagnosed glioblastoma, according to findings from a cohort of the phase II NRG-BN001 trial, which were presented as late-breaking research during the 2025 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract LBA 15).
“We had developed this trial to test the potential survival advantage using proton therapy combined with temozolomide for glioblastoma with the dual hypothesis of the benefit of dose escalation and the sparing effect on lymphocytes in circulation, critical in maintaining an antitumor immune response, and are excited to report that the predefined signal to support the development of a definitive phase III trial of proton dose-escalation for glioblastoma has been achieved,” stated lead study author Minesh P. Mehta, MD, MB, ChB, FASTRO, Deputy Director, John and Mary Lou Dasburg Endowed Chair in Radiation Oncology, and Chair of Radiation Oncology at Baptist Health Miami Cancer Institute, as well as Chair of the Department of Oncological Sciences at the Florida International University Herbert Wertheim College of Medicine.
Rationale and Study Methods
Dose intensification of radiation therapy up to 60 Gy has led to improved survival in patients with glioblastoma. However, early studies have shown that levels higher than 60 Gy did not improve overall survival. Studies for radiation therapy concomitantly with temozolomide have shown that simultaneous integrated boost intensification up to 75 Gy is safe and may prove to be more effective for patients with glioblastoma.
Lymphopenia has been associated with reduced overall survival, although level 1 evidence suggests that proton therapy leads to less lymphopenia.
Researchers conducted a signal-seeking, randomized phase II trial to explore whether simultaneous integrated boost intensification to 75 Gy with photon or proton therapy could improve survival in patients with newly diagnosed glioblastoma. The study included patients with newly diagnosed glioblastoma, Karnofsky performance status of 70, and 5-cm residual tumor/cavity. Patients were randomly assigned in a 1:2 ratio to receive either the control or dose-intensified radiation dose in a photon or proton therapy cohort. Standard concomitant and adjuvant temozolomide was given as well.
Findings from the photon cohort were already published. They showed that the dose-intensified photon radiation therapy did not lead to improved overall survival compared with the control dose.
The proton radiation therapy cohort included 193 patients, and the cohort assumed 80% power to detect a hazard ratio (HR) of 0.72.
Key Study Findings
The dose-intensified arm achieved improved overall survival, with a median of 22.8 months with dose-intensified proton radiation therapy compared with 22 months with standard proton radiation therapy (HR = 0.81; 70% confidence interval [CI] = 0.67–0.98; P = .11). Overall survival findings remained significant even when adjusting for the stratification factors of MGMT methylation status and RPA class. Overall survival was also extended in patients with MGMT methylated disease and for patients with lower RPA class, without significant interactions by treatment arm.
At 2 years, there was an absolute survival improvement of 6.8% favoring the 75-Gy arm over the 60-Gy arm (49.9% vs 43.1%), which was reduced to 4.6% at 3 years (30% vs 25.4%).
No statistically significant differences were observed between the dose arms for high-grade toxicities. The rate of grade 3 lymphopenia was 17.1% in the 75-Gy arm vs 23.4% in the 60-Gy arm, and the rates of grade 4 neurologic toxicities were 5% and 1.8%, respectively.
Disclosure: The study was supported by the National Cancer Institute of the National Institutes of Health. For full disclosures of the study authors, visit amportal.astro.org.
